Tetralones are known for being particularly useful as synthesis intermediates for preparing different serotonin pre-synaptic inhibitor compounds with antidepressant activity. This is described more precisely in U.S. Pat. Nos. 4,029,731 and 4,045,488 and European Patent No. 30,081. Until now, the 4-aryltetralones have been prepared using a method comprising five steps described by Johnson and Daub in Organic Reactions, Vol. VI, pages 1-73 and in European Patent No. 30,081. This method involves (a) the reaction of benzoyl chloride with an aromatic hydrocarbon in the presence of aluminum chloride to form a benzophenone; (b) condensation of said benzophenone under the conditions of the Stobbe reaction in the presence of a strong base, such as potassium tert-butoxide, with diethyl succinate; (c) decarboxylation of the product obtained using an aqueous hydrobromic acid solution to form a 4,4-diarylbutenoic acid; (d) hydrogenation of said acid on palladium/charcoal to form the corresponding 4,4-diarylbutanoic acid; and (e) cyclization of the butanoic acid into a 4-aryltetralone either directly by means of hydrofluoric acid or polyphosphoric acid, or, after transformation into the corresponding acid chloride using thionyl chloride, by the action of aluminum chloride under the conditions of the Friedel-Crafts reaction.
It is clear that this known method has many synthetic drawbacks. In fact, it takes an extended period to complete since it comprises five steps which each require a relatively long reaction time. Moreover, it uses expensive reagents such as potassium tert-butoxide and palladium on charcoal catalyst, or aggressive agents very dangerous to use such as hydrobromic acid, hydrofluoric acid and thionyl chloride. Furthermore, because of the large number of steps required, the overall yield of the tetralone is very low. In the best cases, the yield does not exceed 40% with respect to the starting benzoyl chloride.
A synthesis of the tetralone is described in U.S. Pat. No. 5,019,655 and by I. B. Repinskaya et al., Zhur. Org. Khim., 18, 870 (1982).
The instant process provides a method of going directly to the desired imine intermediate.
The preparation of N-methyl-1-naphthylamine by the palladium on carbon dehydrogenation of the imine formed by the reaction of tetralone with methylamine is not specifically described. The procedure is described in U.S. Pat. Nos. 3,219,702; 3,219,704 and 4,431,841.
The conversion of 4-(3,4-dichlorophenyl)-3,4-dihydro-2H-naphthalen-1-ylidene-methylamine to sertraline is described in U.S. Pat. No. 4,536,518 and by W. M. Welch et al., J. of Medinical Chem. 1984, 27, 1508. A procedure for the preparation of 4-(3,4-dichlorophenyl)-3,4-dihydro-2H-naphthalen-1-ylidene-methylamine which is outside the scope of this invention is described in U.S. Pat. No. 4,855,500.